Lyme disease is a zoonosis caused by the tick-borne spirochaete B. burgdorferi (Steere et al., N. Engl. J. Med., 308:733-740, 1983). When a susceptible host is bitten by an Ixodes tick, B. burgdorferi organisms enter the skin. B. burgdorferi spirochaetes are helically shaped, motile cells with an outer cell membrane that surrounds a protoplasmic cylinder complex, consisting of the cytoplasm, the cell wall, the inner cell membrane and the flagella which are located not at the cell surface but in the periplasmic space between the outer cell membrane and the protoplasmic cylinder. The outer cell membrane and the flagella are assumed to play an important role in the host-parasite interactions during the disease and have been subjected to several investigations, identifying major surface-exposed proteins as important immunogens (Barbour et al., J. Clin. Invest. 72:504-515, 1983).
In humans the initial skin manifestation is termed erythema chronicum migrans (ECM) whereas a long-standing infection of the skin produces acrodermatitis chronica atrophicans (Asbrink et al., Acta Derm. Venereol. 64:506-512, 1984). The Borrelia organisms also enter the circulatory system of the host and are distributed to various organs, including the brain and joints (Barbour et al., Microbiol. Rev. 50:381-400, 1986). A secondary spread of the pathogens produces a variety of clinical syndromes, including lymphocytic meningoradiculitis (Pfister et al., J. Neurol. 118:1-4, 1984), myocarditis (Steere et al., Ann. Intern. Med. 93:8-10, 1980) and chronic arthritis (Steere et al., Ann. Intern. Med. 90:286-291, 1979). In many patients the infection of some tissues, particularly the brain and joints, persists for years and can be severely disabling. These forms of chronic Lyme disease are a consequence of the host's inability to rid itself of the infectious agent and perhaps the development of an autoimmune reaction (Steere et al., Ann. Intern. Med. 99:76-82, 1983).
It has been shown that the earliest IgM antibodies formed against antigens of the B. burgdorferi strain B31, which was deposited in the American Type Culture Collection in 1983 with the Accession No. ATCC 35210, are directed against a genus-specific flagellar polypeptide termed flagellin having a molecular weight of 41 kd (Craft et al., J. Clin. Invest. 78:934-939, 1986) and which reacts with monoclonal antibody H9724 (Barbour et al., Infect. Immun. 52:549-554, 1986). IgG antibodies are also first directed to the 41 kd flagellin, but with advancing disease IgG antibodies form against other immunogens, especially against two abundant proteins with molecular weights of 31 kd and 34 kd. These two proteins, which have been denoted OspA (31 kd) and OspB (34 kd), have been found to be located at the B. burgdorferi surface and embedded in its outer fluid cell membrane (Barbour et al., J. Clin. Invest. 72:504-515, 1983).
U.S. Pat. No. 4,721,617 discloses the use of inactivated whole B. burgdorferi spirochaetes as a vaccine against Lyme disease. In addition, U.S. Pat. No. 6,203,798 teaches the use of protein antigens, OspA and OspB as vaccine candidates. However, as of Feb. 25, 2002, the manufacturer announced that the LYMErix™ Lyme disease vaccine that includes OspA will no longer be commercially available.
Thus, a need remains for a reagent that can be used to produce an immune response against B. burgdorferi, such as a protective immune response, in order to produce an effective vaccine to prevent Lyme disease.